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通过纳米药物递送系统增强肝纤维化治疗效果的递药策略。

Delivery Strategy to Enhance the Therapeutic Efficacy of Liver Fibrosis via Nanoparticle Drug Delivery Systems.

机构信息

Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, China.

出版信息

ACS Nano. 2024 Aug 13;18(32):20861-20885. doi: 10.1021/acsnano.4c02380. Epub 2024 Jul 31.

Abstract

Liver fibrosis (LF) is a pathological repair reaction caused by a chronic liver injury that affects the health of millions of people worldwide, progressing to life-threatening cirrhosis and liver cancer without timely intervention. Due to the complexity of LF pathology, multiple etiological characteristics, and the deposited extracellular matrix, traditional drugs cannot reach appropriate targets in a time-space matching way, thus decreasing the therapeutic effect. Nanoparticle drug delivery systems (NDDS) enable multidrug co-therapy and develop multifactor delivery strategies targeting pathological processes, showing great potential in LF therapy. Based on the pathogenesis and the current clinical treatment status of LF, we systematically elucidate the targeting mechanism of NDDS used in the treatment of LF. Subsequently, we focus on the progress of drug delivery applications for LF, including combined delivery for the liver fibrotic pathological environment, overcoming biological barriers, precise intracellular regulation, and intelligent responsive delivery for the liver fibrotic microenvironment. We hope that this review will inspire the rational design of NDDS for LF in the future in order to provide ideas and methods for promoting LF regression and cure.

摘要

肝纤维化(LF)是一种由慢性肝损伤引起的病理修复反应,影响着全球数百万人的健康,如果不及时干预,它会进展为危及生命的肝硬化和肝癌。由于 LF 病理的复杂性、多种病因特征以及细胞外基质的沉积,传统药物不能以时空匹配的方式达到适当的靶点,从而降低了治疗效果。纳米药物递送系统(NDDS)能够实现多药联合治疗,并针对病理过程开发多因素递药策略,在 LF 治疗方面显示出巨大的潜力。基于 LF 的发病机制和当前临床治疗现状,我们系统地阐明了用于 LF 治疗的 NDDS 的靶向机制。随后,我们重点介绍了 LF 药物递送应用的进展,包括针对肝纤维化病理环境的联合递药、克服生物屏障、精确的细胞内调控以及针对肝纤维化微环境的智能响应递药。我们希望这篇综述能够为未来 LF 的 NDDS 合理设计提供启示和方法,以促进 LF 的逆转和治愈。

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